bristol myerd squibb European Association for the Study of Diabetes (EASD) Highlights

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bristol myerd squibb European Association for the Study of Diabetes (EASD) Highlights

  1. 1. EASD 2008 Highlights Investor Teleconference Sept 9, 2008 1 Not For Promotional Use
  2. 2. Comments will be about the Company’s future plans and prospects that may be forward-looking statements under the Private Securities Litigation Reform Act of 1995. We caution that actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Company’s most recent annual report on Form 10-K, periodic reports on Form 10-Q and current reports on Form 8-K. These documents are available from the SEC, the Bristol-Myers Squibb web site or from Bristol-Myers Squibb Investor Relations. While we may elect to update forward-looking statements at some point in the future, we specifically disclaim any obligation to do so, even if our estimates change. 2 Not For Promotional Use
  3. 3. Diabetes: A Growing, Global Problem Type 2 Diabetes prevalence expected to grow from 190 million to 330 million by 2030 Europe prevalence is Diabetes growing rapidly lower (~4.6%), but in U.S. – current increasing, especially in prevalence rate 6.7% the southern countries Mexico – highest India and China will make up prevalence rates in nearly 50% of the total the world: 12.4% number of patients with diabetes in 2030 Source: WHO 3 Not For Promotional Use 3
  4. 4. Majority of Patients Are Not Optimally Controlled Percentage of patients not controlled, 100 by market (relative to HbA1c Target of 7.0%) 60% of 80 69 US diabetic 64 62 Patients (%) patients 58 57 60 51 do not know their A1c or 40 FPG values 20 0 UK FR GER ITL SPN US Source: Adelphi, 2006 Disease Specific Programmes, NHWS 2006 4 Not For Promotional Use
  5. 5. The Progressive Nature of Type 2 Diabetes Ultimately Overwhelms Medications Glycemic Control in an Illustrative Patient Potential = Slope 5 treatment p er 0.75% change yrs. First 5yr s Agent Goal* HbA1c A1c=<7 Goal** A1c=<6.5 Normal*** A1c=5% ~30 Years There remains a need for new therapies Sources: ADOPT, UKPDS (*) According to the ADA; (**) according to the AACE/ACE; (***) according to the NIH 5 Not For Promotional Use
  6. 6. EASD 2008: Dapagliflozin Data on dapagliflozin was presented from the largest and longest (12 weeks) trial of an SGLT2 Renal Glucose Reabsorption Inhibitor to date. Results demonstrated that dapagliflozin: Induced controlled glucosuria Improved glycemic control – Reduced fasting glucose – Reduced postprandial glucose – Reduced HbA1c Lowered weight Showed little propensity to cause hypoglycemia Demonstrated no clear adverse safety or tolerability signals over 12 weeks Phase 2 Study, EASD Sept 2008 6 Not For Promotional Use
  7. 7. Saxagliptin Overview Specifically designed to be a selective inhibitor with extended binding to the DPP-4 enzyme Completed Phase 3 registrational program New Drug Application officially filed by the FDA Marketing Authorization Application accepted for review by the EMEA 7 Not For Promotional Use
  8. 8. Patient Exposures Throughout Saxagliptin Program Phase 1 and 2 ~110 subjects exposed to saxagliptin at 20-80x the 5 mg dose for up to 6 weeks ~670 subjects exposed to saxagliptin at 2-10x the 5 mg dose for up to 12 weeks Phase 3 ~1000 patients treated at 10 mg dose for up to 2 years >3000 patients treated at any dose in Phase 3 8 Not For Promotional Use
  9. 9. Saxagliptin Profile is Competitive Produced significant reductions in all key measures of glucose control in treatment naïve patients and patients treated with commonly used oral agents Generally well tolerated in clinical trials across all usage situations – Clinical correlates to the skin lesions in monkeys have not been identified in human clinical trials of saxagliptin Life cycle program underway 9 Not For Promotional Use
  10. 10. Saxagliptin Initial Combination with Metformin Design: EASD 2008 1 Wk PBO 24 Wks N=1306 Lead-in PBO + MET IR (with titration)*† Treatment-Naïve T2D SAXA 10 mg + PBO† Superiority Test (HbA1C ≥8%-≤12%) SAXA 5 mg + MET IR (with titration)*† Superiority Test SAXA 10 mg + MET IR (with titration)*† *MET IR titration: Forced titration from 500 mg to 1000 mg at wk 1, then elective titration at wks 2, 3, 4, and 5 to achieve mean fasting plasma glucose (FPG) <110 mg/dL (maximum MET 2000 mg total daily dose). †Ifrescue criteria met in short term, add pioglitazone 15-45 mg o.d. and enter long-term phase; pioglitazone rescue also available in long-term extension. Phase 3 Study -039, EASD Sept 2008 10 Not For Promotional Use
  11. 11. HbA1C Adjusted Mean Changes from Baseline at Week 24* Saxagliptin (mg) Dose 5 + Met 10 + Met 10 Met n= 306 315 317 313 Baseline mean (%) 9.4 9.5 9.6 9.4 0.0 -0.5 -1.0 Δ HbA1C (%) with 95% CI -1.5 -1.7 -2.0 -2.0 -2.5 -2.5 †‡ -2.5 †‡ -3.0 *LOCF=last observation carried forward †P<.0001 vs Saxa 10 mg ‡P<.0001 vs Met Phase 3 Study -039, EASD Sept 2008 11 Not For Promotional Use
  12. 12. Patients Achieving Therapeutic Glycemic Response (HbA1C ≤6.5% and <7%) at Week 24* 60 Patients Achieving 40 Glycemic Response (%) with 95% CI 20 45.3† 60.3† 40.6‡ 59.7† 20.3 32.2 29.0 41.1 ≤6.5% <7.0% ≤6.5% <7.0% ≤6.5% <7.0% ≤6.5% <7.0% 0 Saxa 5 mg Saxa 10 mg Saxa 10 mg Met + Met + Met n = 320 n = 314 n = 307 n = 315 *LOCF †P<.0001 vs Saxa 10 mg and vs Met ‡P <.0001 vs Saxa 10 mg and P =.0026 vs Met Phase 3 Study -039, EASD Sept 2008 12 Not For Promotional Use
  13. 13. HbA1C Adjusted Mean Change: Subgroup Analysis by Baseline HbA1C Baseline HbA1C <8% ≥8%-<9% ≥9%-<10% ≥10% 0.0 -0.5 Δ HbA1C (%) with 95% CI -0.5 -1.0 -1.0 -1.0 -1.1 -1.2 -1.5 -1.4 -1.5 -2.0 -1.9 -2.0 -2.0 -2.5 -2.5 -2.5 -2.5 -2.7 -3.0 -3.3 -3.3 -3.5 Saxagliptin + Met -4.0 5 mg 10 mg Saxa 10 mg Met Phase 3 Study -039, EASD Sept 2008 13 Not For Promotional Use
  14. 14. FPG Adjusted Mean Changes from Baseline at Week 24* Saxagliptin (mg) Dose 5 + Met 10 + Met 10 Met n= 315 317 327 320 Baseline mean (mg/dL) 198.9 204.3 200.9 199.1 0 -10 -20 Δ FPG (mg/dL) -30 -31 with 95% CI -40 -50 -47 -60 -60 †‡ -62 † § *LOCF -70 †P<.0001 vs Saxa 10 mg ‡P=.0002 vs Met §P<.0001 vs Met Phase 3 Study -039, EASD Sept 2008 14 Not For Promotional Use
  15. 15. Most Common (≥5%) Reported Adverse Events Saxa 5 mg Saxa 10 mg Saxa + Met + Met 10 mg Met n=320 n=323 n=335 n=328 Total patients with 177 (55.3) 185 (57.3) 179 (53.4) 192 (58.5) at least 1 AE, n (%) Nasopharyngitis 22 (6.9) 8 (2.5) 14 (4.2) 13 (4.0) Headache 24 (7.5) 32 (9.9) 21 (6.3) 17 (5.2) Diarrhea 22 (6.9) 31 (9.6) 10 (3.0) 24 (7.3) Hypertension 15 (4.7) 17 (5.3) 15 (4.5) 11 (3.4) Phase 3 Study -039, EASD Sept 2008 15 Not For Promotional Use
  16. 16. Conclusions Saxagliptin, given in combination with metformin as initial therapy, led to clinically relevant improvements that were significantly greater than either treatment alone across all key glycemic parameters studied including: – HbA1C – FPG – Proportion of patients with HbA1C <7% – PPG during OGTT Saxagliptin, given in combination with metformin as initial therapy, was well tolerated over the course of the study Phase 3 Study -039, EASD Sept 2008 16 Not For Promotional Use
  17. 17. Saxagliptin Add-on TZD Study Design: EASD 2008 2-Wk TZD + PBO Lead-in 12 Months LTE 24 Wk (N=565) PBO + TZD* PBO + TZD* Stable Dose TZD†‡ ≥12 Wk Superiority T2D SAXA 5 mg o.d. + TZD* SAXA 5 mg o.d. + TZD* HbA1c ≥7.0%–≤10.5% Superiority SAXA 2.5 mg o.d. + TZD* SAXA 2.5 mg o.d. + TZD* *If rescue criteria met in short-term phase, add metformin 500–2500 mg total daily dose, and enter LTE phase; metformin rescue was also available in the LTE phase. †Stabledose of TZD defined as pio 30 or 45 mg total daily dose or rosi 4 or 8 mg total daily dose. TZD dose at entry fixed for duration of study. ‡If determined to be medically appropriate, a switch from rosi to pio was permitted. [CSR Fig 3.1] Phase 3 Study -013, EASD Sept 2008 17 Not For Promotional Use
  18. 18. HbA1C Adjusted Mean Change from Baseline at Week 24 (LOCF) Saxagliptin (mg) + TZD Dose 2.5 5 Pbo + TZD n= 192 183 180 Baseline Mean 8.25 8.35 8.19 -0.1 -0.3 -0.3 -0.5 Δ HbA1C (%) Source: CV181013 – Figure 7.2.1A with 95% CI -0.7 -0.7 p = .0007 -0.9 -0.9 -1.1 p <.0001 Phase 3 Study -013, EASD Sept 2008 18 Not For Promotional Use
  19. 19. Fasting Plasma Glucose Adjusted Mean Change from Baseline at Week 24 (LOCF) Saxagliptin (mg) + TZD Dose 2.5 5 Pbo + TZD n= 193 185 181 163.0 159.5 162.4 Baseline Mean (mg/dL) 5.0 0.0 -2.8 -5.0 Δ FPG (mg/dL) Source: CV181013 – Figure 7.3.1A -10.0 with 95% CI -15.0 -14.3 -17.3 -20.0 p = .0053 p = .0005 -25.0 Phase 3 Study -013, EASD Sept 2008 19 Not For Promotional Use
  20. 20. Postprandial Glucose AUC Adjusted Mean Change from Baseline at Week 24 (LOCF) Saxagliptin (mg) + TZD Dose 2.5 5 Pbo + TZD n= 151 131 123 48301 47866 47256 Baseline Mean (mg min/dL) 0 -2000 -2690 -4000 Δ PPG AUC (mg min/dL) -6000 with 95% CI CV181013 – Figure 7.3.3 -8000 -7849 -9269 -10000 p <.0001 p <.0001 -12000 Phase 3 Study -013, EASD Sept 2008 20 Not For Promotional Use
  21. 21. Most Common (≥5%) Reported Adverse Events During 24-Week Treatment Saxa 2.5 mg Saxa 5 mg All Saxa Pbo + TZD + TZD + TZD + TZD N = 184 N = 195 N = 186 N = 381 Total subjects with AE 121 (62.1) 138 (74.2) 259 (68.0) 123 (66.8) Adverse Events (≥ 5%) Upper respiratory tract 15 (7.7) 17 (9.1) 13 (7.1) 32 (8.4) infection Urinary tract infection 7 (3.6) 12 (6.5) 12 (6.5) 19 (5.0) Nasopharyngitis 6 (3.1) 9 (4.8) 15 (3.9) 11 (6.0) Arthralgia or joint pain 11 (5.6) 5 (2.7) 16 (4.2) 5 (2.7) Headache 9 (4.6) 10 (5.4) 19 (5.0) 7 (3.8) Dizziness 5 (2.6) 6 (3.2) 11 (2.9) 10 (5.4) Oedema peripheral 6 (3.1) 15 (8.1) 21 (5.5) 8 (4.3) Hypertension 11 (5.6) 8 (4.3) 19 (5.0) 9 (4.9) Phase 3 Study -013, EASD Sept 2008 21 Not For Promotional Use
  22. 22. Conclusions In patients with type 2 diabetes not achieving glycemic control on TZD monotherapy, the addition of saxagliptin provided statistically significant and clinically meaningful improvements in the key parameters of glycemic control. Significantly more patients achieved the HbA1C target of <7% at week 24 with saxagliptin added to TZD therapy vs TZD monotherapy. Over 24 weeks, the combination of saxagliptin and TZD was generally well tolerated. Phase 3 Study -013, EASD Sept 2008 22 Not For Promotional Use
  23. 23. Saxagliptin Add-on SU Study Design: EASD 2008 24 Weeks (N=768) 12 Months LTE 4 Weeks GLY 7.5 mg + PBO Lead-in UP-GLY 10/15/20 mg* o.d. + PBO† UP-GLY 10/15 mg* o.d. + PBO† T2D SU Monotherapy ≥2 months Superiority Submaximal SU GLY 7.5 mg o.d. + SAXA 2.5 mg o.d.† GLY 7.5 mg o.d. + SAXA 2.5 mg o.d.† HbA1c ≥7.5%–≤10.0% Superiority to Enroll MFPG ≥140 mg/dL or GLY 7.5 mg o.d. + SAXA 5 mg o.d.† GLY 7.5 mg o.d. + SAXA 5 mg o.d.† MFWBG ≥131 mg/dL and HbA1c ≥7.0% to Randomize •92% reached maximum allowed dose of Glyburide in the short term phase (UP-GLY) - per the protocol titration (UP- criteria †If rescue criteria was met in short-term phase, add metformin 500–2500 mg TDD and enter LTE phase; metformin rescue also available in the LTE phase. MFPG = mean fasting plasma glucose; MFWBG = mean fasting whole blood glucose; o.d. = once daily. Phase 3 Study -040, EASD Sept 2008 23 Not For Promotional Use
  24. 24. HbA1C Adjusted Mean Change from Baseline at Week 24 (LOCF) Saxagliptin (mg) + Gly Dose 2.5 5 Pbo + UP-Gly n= 246 250 264 Baseline Mean 8.36 8.48 8.44 0.2 +0.1 0.0 Δ HbA1C (%) -0.2 with 95% CI Source: CV181040 – Figure 7.2.1A -0.4 -0.5 -0.6 -0.6 p <.0001 -0.8 p <.0001 Phase 3 Study -040, EASD Sept 2008 24 Not For Promotional Use
  25. 25. Fasting Plasma Glucose Adjusted Mean Change from Baseline at Week 24 (LOCF) Saxagliptin (mg) + Gly Dose 2.5 5 Pbo + UP-Gly n= 247 252 265 170.1 175.0 Baseline Mean (mg/dL) 174.4 5.0 0.7 0.0 Δ FPG (mg/dL) Source: CV181040 – Figure 7.3.1A -5.0 with 95% CI -7.1 -10.0 -9.7 p = .0218 -15.0 p = .0020 Phase 3 Study -040, EASD Sept 2008 25 Not For Promotional Use
  26. 26. Postprandial Glucose AUC Adjusted Mean Change from Baseline at Week 24 (LOCF) Saxagliptin (mg) + Gly 2.5 5 Pbo + UP-Gly Dose 190 195 204 n= 49124 50342 51801 Baseline Mean (mg min/dL) 1196 1500 -500 Δ PPG AUC (mg min/dL) -2500 CV181040 – Figure 7.3.3 with 95% CI -4500 -4296 -5000 p <.0001 -6500 p <.0001 Phase 3 Study -040, EASD Sept 2008 26 Not For Promotional Use
  27. 27. Most Common (≥5%) Reported Adverse Events During 24-Week Treatment Pbo Saxa 2.5 mg Saxa 5 mg All Saxa + Up-Gly + Gly + Gly + Gly N = 267 N = 248 N = 253 N = 501 Total subjects with AE 186 (75.0) 183 (72.3) 369 (73.7) 205 (76.8) Adverse Events (≥5%)* Urinary tract infection 13 (5.2) 27 (10.7) 40 (8.0) 22 (8.2) Nasopharyngitis 14 (5.6) 15 (5.9) 29 (5.8) 18 (6.7) Upper respiratory tract 11 (4.4) 16 (6.3) 27 (5.4) 18 (6.7) infection Influenza 13 (5.2) 10 (4.0) 23 (4.6) 16 (6.0) Diarrhoea 14 (5.6) 10 (4.0) 24 (4.8) 14 (5.2) Back pain 12 (4.8) 15 (5.9) 27 (5.4) 12 (4.5) Pain in extremity 11 (4.4) 9 (3.6) 20 (4.0) 15 (5.6) Headache 19 (7.7) 19 (7.5) 38 (7.6) 15 (5.6) Cough 13 (5.2) 10 (4.0) 23 (4.6) 13 (4.9) Hypertension 9 (3.6) 16 (6.3) 25 (5.0) 6 (2.2) *Excludes Hypoglycemia Hypoglycemic events were reported in 13.3% [33/248], 14.6% [37/253] of subjects in the • SAXA 2.5-mg & 5-mg treatment groups vs Up-Gly (10.1% [27/267]). The differences were not statistically significant Phase 3 Study -040, EASD Sept 2008 27 Not For Promotional Use
  28. 28. Conclusions In patients with type 2 diabetes not achieving glycemic control on submaximal doses of glyburide monotherapy, the addition of saxagliptin once daily provided statistically significant and clinically meaningful reductions in the key parameters of glycemic control in contrast to up-titrated glyburide monotherapy. More than twice as many patients treated with the combination of saxagliptin and submaximal dose of glyburide achieved target HbA1c <7.0% compared with up-titrated glyburide. Improvements in glycemic parameters with the addition of saxagliptin to a submaximal dose of glyburide were achieved without any significant increases in hypoglycemia. The administration of saxagliptin in combination with submaximal doses of glyburide for up to 24 weeks was generally well tolerated. Phase 3 Study -040, EASD Sept 2008 28 Not For Promotional Use
  29. 29. Saxagliptin Conclusion – EASD Highlights Clinically Meaningful Reductions in All Key Measures of Glucose Control Studied Given in combination with metformin as an initial therapy, 5mg saxagliptin demonstrated A1c reductions of 2.5% from baseline – In patients with very high (≥10%) A1c’s, saxagliptin 5mg plus metformin demonstrated A1c reductions of 3.3% from baseline When added to TZD, saxagliptin 5mg demonstrated A1c reduction of 0.9% from baseline When given in combination with an SU, saxagliptin 5mg demonstrated A1c reduction of 0.6% – No statistically significant increase in hypoglycemia Saxagliptin also produced significant reductions in FPG and PPG Saxagliptin was well tolerated in all usage situations 29 Not For Promotional Use
  30. 30. EASD 2008 Highlights Investor Teleconference Sept 9, 2008 30 Not For Promotional Use

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